title: Clinicopathological findings in non-human primate recipients of porcine renal xenografts: quantitative and qualitative evaluation of proteinuria.
abstract: BACKGROUND
  Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. The detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential graft rejection. In this study, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function was supported only by the transplanted organ.
  
  
  METHODS
  Eight bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a single kidney from α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59, and α1,2-fucosyltransferase. In addition to hematological and biochemical analyses, quantitative and qualitative analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE), respectively.
  
  
  RESULTS
  The main hematological and biochemical changes recorded after transplantation were a progressive anemia and a severe and progressive decrease in total proteins. In urine samples, the UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation, but bands consistent with mixed (i.e., tubular and glomerular) proteinuria were observed in all samples collected post-transplantation.
  
  
  CONCLUSIONS
  The study of clinicopathological changes in cynomolgus monkey renal xenograft recipients provides a valid help in monitoring the health conditions in the post-transplant period. Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey renal xenograft recipients may be considered a valid, inexpensive, and less time-consuming method than more sophisticated techniques in monitoring proteinuria. Proteinuria and presence of low molecular weight (LMW) proteins were consistently found in urine after transplantation, independent of fluctuations in renal function.
authors.affiliation: Department of Comparative Biomedicine and Nutrition, University of Padua, Legnaro, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pintore
authors.forename: Saverio
authors.initials: S
authors.lastname: Paltrinieri
authors.forename: Marta
authors.initials: M
authors.lastname: Vadori
authors.forename: Federica
authors.initials: F
authors.lastname: Besenzon
authors.forename: Laura
authors.initials: L
authors.lastname: Cavicchioli
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: De Benedictis
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cozzi
authors.forename: Mark B
authors.initials: MB
authors.lastname: Nottle
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnaro
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics; D001081:Apyrase / Q000235:genetics; D018958:CD55 Antigens / Q000235:genetics; D018957:CD59 Antigens / Q000235:genetics; D003404:Creatinine / Q000652:urine; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D055786:Gene Knockout Techniques; D064593:Heterografts / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008252:Macaca fascicularis; D023421:Models, Animal; D011323:Primates; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification; D011507:Proteinuria / Q000209:etiology* / Q000473:pathology / Q000652:urine; D034421:Sus scrofa; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D015703:Antigens, CD; D001081:Apyrase; D018958:CD55 Antigens; D018957:CD59 Antigens; D003404:Creatinine; D005647:Fucosyltransferases; D005700:Galactosyltransferases; D011506:Proteins; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C051590:CD59 protein, human; C530267:alpha-1,3-galactosyltransferase 1, porcine; C067869:CD39 antigen
keywords: SDS-AGE; primate; proteinuria; renal xenograft